U.S. patent application number 11/574181 was filed with the patent office on 2007-12-20 for optical analysis system with background signal compensation.
This patent application is currently assigned to Koninklijke Philips Electronics N.V.. Invention is credited to Bernardus Leonardus Gerardus Bakker, Wouter Harry Jacinth Rensen, Michael Cornelis Van Beek.
Application Number | 20070291251 11/574181 |
Document ID | / |
Family ID | 35219447 |
Filed Date | 2007-12-20 |
United States Patent
Application |
20070291251 |
Kind Code |
A1 |
Rensen; Wouter Harry Jacinth ;
et al. |
December 20, 2007 |
Optical Analysis System With Background Signal Compensation
Abstract
The invention provides an optical analysis system for efficient
compensation of spectroscopic broadband back-ground, such as
spectroscopic fluorescence background or background signals that
are due to the dark current of a detector. The optical analysis
system effectively provides multivariate optical analysis of a
spectroscopic signal. It provides wavelength selective detection of
various spectral components that are indicative of a superposition
of spectroscopic peaks or bands and their broadband background.
Additionally, the optical analysis system is adapted to acquire
spectral components that predominantly correspond to the broadband
background of the spectroscopic peaks or bands. Wavelength
selective selection of various spectral components is performed on
the basis of reconfigurable multivariate optical elements or on the
basis of a position displacement of a spatial optical transmission
mask.
Inventors: |
Rensen; Wouter Harry Jacinth;
(Eindhoven, NL) ; Bakker; Bernardus Leonardus
Gerardus; (Eindhoven, NL) ; Van Beek; Michael
Cornelis; (Eindhoven, NL) |
Correspondence
Address: |
PHILIPS INTELLECTUAL PROPERTY & STANDARDS
595 MINER ROAD
CLEVELAND
OH
44143
US
|
Assignee: |
Koninklijke Philips Electronics
N.V.
Groenewoudseweg 1
Eindhoven
NL
5621 BA
|
Family ID: |
35219447 |
Appl. No.: |
11/574181 |
Filed: |
August 24, 2005 |
PCT Filed: |
August 24, 2005 |
PCT NO: |
PCT/IB05/52765 |
371 Date: |
February 23, 2007 |
Current U.S.
Class: |
356/39 ; 356/301;
356/307; 356/73; 702/85 |
Current CPC
Class: |
G01J 3/30 20130101; G01J
3/02 20130101; G01J 3/0229 20130101; G01J 3/32 20130101; G01J 3/44
20130101 |
Class at
Publication: |
356/039 ;
356/073; 702/085 |
International
Class: |
G01N 33/48 20060101
G01N033/48; G01N 21/00 20060101 G01N021/00; G06F 19/00 20060101
G06F019/00 |
Foreign Application Data
Date |
Code |
Application Number |
Aug 27, 2004 |
EP |
04104123.7 |
Claims
1. An optical analysis system for determining a principal component
of an optical signal, the optical analysis system comprising: a
dispersive optical element for spatially separating spectral
components of the optical signal in a first direction, spatial
light manipulation means for at least partially transmitting at
least a first spectral component of the optical signal at a first
time and for transmitting at least a second spectral component of
the optical signal at a second time, a detector for detecting the
at least first and second transmitted spectral components,
processing means for performing a correction on the optical signal
on the basis of the at least first and second detected spectral
components.
2. An optical analysis system for determining a principal component
of an optical signal, the optical analysis system comprising: a
dispersive optical element for spatially separating spectral
components of the optical signal in a first direction, a spatial
light manipulator for at least partially transmitting at least a
first spectral component of the optical signal at a first time and
for transmitting at least a second spectral component of the
optical signal at a second time, a detector for detecting the at
least first and second transmitted spectral components, processing
module for performing a correction on the optical signal on the
basis of the at least first and second detected spectral
components.
3. The optical analysis system according to claim 1 wherein the
spatial light manipulation means is shiftable along the first
direction and further comprise a fixed transmission aperture.
4. The optical analysis system according to claim 1, wherein the
spatial light manipulation means comprises a reconfigurable spatial
light modulator.
5. The optical analysis system according to claim 1 wherein the
spatial light manipulation means further comprises an aperture
having at least a first slit, the width of the at least first slit
being modifiable.
6. The optical analysis system according to claim 5, wherein the
spatial light manipulation means further comprises at least a
second slit aperture, the at least first and second slits being
simultaneously shiftable along the first direction.
7. The optical analysis system according to claim 4, the
reconfigurable spatial light manipulation means forms a slit
aperture moving along the first direction.
8. The optical analysis system according to claim 1 wherein the
dispersive optical element and the spatial light manipulation means
form a multivariate optical element, wherein the spatial light
manipulation means is a liquid crystal light modulator or or a
digital micro-mirror device.
9. The optical analysis system according to claim 1 wherein the
system provides non-invasive analysis of blood of a person and
wherein the principal component of the optical signal indicates the
concentration of a substance of the blood.
10. A method of performing a correction on an optical signal of an
optical analysis system, the method comprising the steps of:
spatially separating spectral components of the optical signal in a
first direction by means of a dispersive optical element, at least
partially transmitting at least a first spectral component of the
optical signal at a first time and at least partially transmitting
at least a second spectral component of the optical signal at a
second time, partially transmitting of first and second spectral
components being provided by a spatial light manipulator, detecting
the at least first and second transmitted spectral components by
means of a detector, processing of the at least first and second
detected spectral components for performing the correction on the
optical signal.
11. The method according to claim 10, further comprising the steps
of: at least partially transmitting at least a third spectral
component of the optical signal at the first time, at least
partially transmitting at least a fourth spectral component of the
optical signal at the second time, performing of the correction of
the optical signal being further based on comparing the at least
first, second, third and fourth transmitted spectral
components.
12. A computer program product for performing a correction on an
optical signal of an optical analysis system, the optical signal
being spatially decomposed into its spectral components by means of
a dispersive optical elemental, the computer program product
comprising computer program means being adapted to: control a
spatial light manipulator for at least partially transmitting at
least a first spectral component of the optical signal at a first
time and for at least partially transmitting at least a second
spectral component of the optical signal at a second time, process
an at least first and second electrical signal for performing a
correction on the optical signal, the at least first and second
electrical signals being provided by a detector in response to
detect the at least first and second transmitted spectral
components of the optical signal.
13. The optical analysis system according to claim 2, wherein the
spatial light manipulator is shiftable along the first direction
and further comprise a fixed transmission aperture.
14. The optical analysis system according to claim 1, wherein the
spatial light manipulator comprises a reconfigurable spatial light
modulator.
15. The optical analysis system according to claim 2, wherein the
spatial light manipulator further comprises an aperture having at
least a first slit, the width of the at least first slit being
modifiable.
16. The optical analysis system according to claim 15, wherein the
spatial light manipulator further comprises at least a second slit
aperture, the at least first and second slits being simultaneously
shiftable along the first direction.
17. The optical analysis system according to claim 14, the
reconfigurable spatial light modulator being forms a slit aperture
moving along the first direction.
18. The optical analysis system according to claim 2, wherein the
dispersive optical element and the spatial light manipulator form a
multivariate optical element, wherein the spatial light manipulator
is a liquid crystal light modulator or a digital micro-mirror
device.
19. The optical analysis system according to claim 2, wherein the
system provides non-invasive analysis of blood of a person and
wherein the principal component of the optical signal indicates the
concentration of a substance of the blood.
20. The method of claim 10 further comprising shifting a component
that determines the first spectral component of the optical signal
transmitted to a location to position that allows the second
spectral component of optical signal to be transmitted.
Description
[0001] The present invention relates to the field of optical
spectroscopy.
[0002] Spectroscopic techniques are widely used for determination
of the composition of a substance. By spectrally analyzing an
optical signal, i.e. a spectroscopic optical signal, the
concentration of a particular compound of the substance can be
precisely determined. The concentration of a particular substance
is typically given by an amplitude of a principal component of an
optical signal.
[0003] U.S. Pat. No. 6198,531 B1 discloses an embodiment of an
optical analysis system for determining an amplitude of a principal
component of an optical signal. The known optical analysis system
is part of a spectroscopic analysis system suited for, e.g.,
analyzing which compounds are comprised at which concentrations in
a sample. It is well known that light interacting with the sample
carries away information about the compounds and their
concentrations. The underlying physical processes are exploited in
optical spectroscopic techniques in which light of a light source
such as, e.g., a laser, a lamp or light emitting diode is directed
to the sample for generating an optical signal which carries this
information.
[0004] For example, light may be absorbed by the sample.
Alternatively or in addition, light of a known wavelength may
interact with the sample and thereby generate light at a different
wavelength due to, e.g. a Raman process. The transmitted and/or
generated light then constitutes the optical signal which may also
be referred to as the spectrum. The relative intensity of the
optical signal as function of the wavelength is then indicative for
the compounds comprised in the sample and their concentrations.
[0005] To identify the compounds comprised in the sample and to
determine their concentrations the optical signal has to be
analyzed. In the known optical analysis system the optical signal
is analyzed by dedicated hardware comprising an optical filter.
This optical filter has a transmission which depends on the
wavelength, i.e. it is designed to weight the optical signal by a
spectral weighting function which is given by the wavelength
dependent transmission. The spectral weighting function is chosen
such that the total intensity of the weighted optical signal, i.e.
of the light transmitted by the filter, is directly proportional to
the concentration of a particular compound. Such an optical filter
is also denoted as multivariate optical element (MOE). This
intensity can then be conveniently detected by a detector such as,
e.g., a photodiode. For every compound a dedicated optical filter
with a characteristic spectral weighting function is used. The
optical filter may be, e.g., an interference filter having a
transmission constituting the desired weighting function.
[0006] Typically, the principal component comprises a positive part
and a negative part. Therefore, a part of the optical signal is
directed to a first filter which weights the optical signal by a
first spectral weighting function corresponding to the positive
part of the principal component, and a further part of the optical
signal is directed to a second filter which weights the optical
signal by a second spectral weighting function corresponding to the
negative part of the principal component. The light transmitted by
the first and second filters is then separately detected by a first
and a second detector, respectively. The two signals obtained by
the two detectors are then subtracted, resulting in a signal with
an amplitude corresponding to the concentration of a dedicated
compound of the sample.
[0007] In this way, instead of the entire spectrum, only a single
signal that is proportional to a specific compound of the sample is
detected. Hence, a rather expensive charge coupled device
(CCD)--camera can be effectively replaced by low-cost light
sensitive detectors, such as e.g. semi-conductor based
photodiodes.
[0008] In many spectroscopic analysis systems elastically scattered
radiation as well as dark current of the detector may give rise to
appreciable background signals that are superimposed to the
intrinsic spectroscopic signal. Typically, spectroscopic signals
that have to be analyzed feature relatively narrow peaks in the
spectrum compared to the broadband fluorescence or dark current
background. Generally, a reliable and sufficient spectroscopic
analysis requires effective elimination of broadband background
signals.
[0009] This can for example be provided by filtering of slowly
varying signal components of a spectrum. However, by making use of
MOE's only a single signal rather than the entire spectrum is
detected. Consequently, a filtering of slowly varying spectral
components cannot be performed in a straightforward way. However,
background compensation is a necessary step of spectroscopic signal
analysis and it also has to be applied on spectroscopic analysis
based on multivariate optical analysis.
[0010] The advantages of a background compensation scheme are
obvious, when for example the background is subject to
modifications which might easily occur in the framework of
spectroscopic analysis of biological tissue. In particular, when
spectroscopic analysis is applied to a variety of different
biological tissues featuring different optical properties, a
fluorescence background may strongly depend on the type of the
biological tissue. Moreover, other effects like scattering of light
in a light guiding arrangement providing transmission of collected
optical signals to a spectroscopic analysis system may also have a
major impact on the background level. Also, when the background is
non uniform, i.e. the fluorescence or dark current is non uniform
over a large spectral range, subtracting a constant fluorescence
and dark current background would severely falsify the
spectroscopic signal to a large extent.
[0011] The present invention therefore aims to provide background
correction of an optical spectrum on the basis of multivariate
optical elements.
[0012] The present invention provides an optical analysis system
for determining a principal component of an optical signal. The
optical analysis system comprises a dispersive optical element,
spatial light manipulation means, a detector and processing means.
The dispersive optical element serves to spatially separate
spectral components of the optical signal in a first direction.
Typically, the dispersive optical element is implemented as a
grating or prism. The spatial light manipulation means serve to at
least partially transmitting at least a first spectral component of
the optical signal at a first time and for transmitting at least a
second spectral component of the optical signal at a second
time.
[0013] The at least first and second transmitted spectral
components of the optical signal are then detected by means of the
detector. Hence, the at least first and second transmitted spectral
components are sequentially detected at the first and the second
time. In this way the detector serves to detect at least a first
and at least a second transmitted spectral component of the optical
signal in a sequential way. The processing means are adapted to
perform a correction on the optical signal on the basis of the at
least first and second detected spectral components. In a strict
sense the processing means are adapted to perform the correction on
electrical signals that are obtained from the detector in response
to detect the at least first and second transmitted spectral
components.
[0014] The invention is particularly based on the assumption, that
the optical signal comprises a broadband background and narrow band
spectroscopic peaks that are relevant for the determination of the
principal component of the optical signal. Furthermore, since the
wavelength of compound specific spectroscopic peaks is known, the
spatial light manipulation means may serve to selectively transmit
only a distinct spectral band that substantially comprises a
particular spectroscopic peak. For example, the first transmitted
spectral component of the optical signal may correspond to a narrow
Raman band.
[0015] Actually the corresponding signal being detected by means of
the detector at the first time comprises a contribution from the
broadband background as well as a contribution from the narrow
Raman band. Hence, the first spectral component of the optical
signal that is transmitted by the spatial light manipulation means
at a first time represents a superposition of a broadband
background and a narrow band spectroscopic signal.
[0016] In order to decompose and to separately resolve the Raman
and the background contribution of the transmitted first spectral
component of the optical signal, the background level has to be
determined and subtracted from the detected first spectral
component. Therefore, the spatial light manipulation means provide
transmitting of at least a second spectral component of the optical
signal at a second time. Here, the spatial light manipulation means
are configured in such a way, that the second spectral component of
the optical signal does not comprise the desired Raman contribution
but exclusively corresponds to a background signal that is
comparable to the background contribution of the first spectral
component being transmitted by the spatial light manipulation means
at the first time. Typically, the second spectral component is only
slightly shifted compared to the first spectral component in such a
way, that it covers a spectral band that is adjacently located to
the first spectral band of the first spectral component.
[0017] According to a further preferred embodiment of the
invention, the spatial light manipulation means are shiftable along
the first direction and further comprise a fixed transmission
aperture. In this basic embodiment the spatial light manipulation
means can be effectively realized in form of a slit aperture that
is shiftable along the first direction, i.e. along the direction of
spatial decomposition of the optical signal or the direction of the
spectrum evolving from the dispersive optical element. For example,
the spatial light manipulation means can be realized as a spatial
transmission mask featuring a plurality of slit apertures, where
each slit corresponds to a distinct Raman band. In this way the
spatial transmission mask serves to transmit a plurality of Raman
peaks whereas other spectral components of the optical signal are
blocked. Since the transmitted Raman peaks typically comprise a
significant contribution of fluorescence and noise background, the
spectroscopic contribution, e.g. the Raman contribution of the
transmitted spectral components has to be extracted. By slightly
shifting the spatial light transmission mask in the direction of
the spectrum of the optical signal, such that the spectroscopic
peaks are substantially blocked by the spatial light transmission
mask and that a neighboring background level is transmitted, the
evolving signal that can be consequently detected by means of the
detector may merely corresponds to the background contribution of
the previously recorded spectroscopic signal. By mutually
subtracting these two sequentially recorded signals the
spectroscopic contribution can be sufficiently resolved.
[0018] Alternatively, instead of shifting the spatial light
manipulation means also the dispersive optical element might be
subject to e.g. rotation, such that the transverse position of the
spectroscopic peaks can be shifted with respect to the slit
apertures of the spatial light manipulation means. In this way
either the spatial light manipulation means or the spectrum in its
entirety has to be, e.g. transversally, shifted. This mutual
shifting can in principle be realized by a manifold of optical
arrangements, that provide changing the direction of the incident
optical signal by appropriately shifting or tilting of any of the
involved optical components. It should only be guaranteed that
during detection of the at least first transmitted spectral
component the spatial position of spectroscopic peaks of the
optical signal substantially match the position of various
apertures of the spatial light manipulation means.
[0019] In contrast, during acquisition of the at least second
transmitted spectral component of the optical signal, the
spectroscopic peaks of the optical signal should be blocked by
means of the spatial light manipulation means and only adjacently
located spectral bands corresponding to background fluorescence or
background noise should be transmitted by means of the spatial
light manipulation means.
[0020] According to a further preferred embodiment of the
invention, the spatial light manipulation means comprise a
reconfigurable spatial light modulator. By implementing the spatial
light manipulation means as a reconfigurable spatial light
modulator, the spatial light manipulation means can be rigidly
fixed in the optical analysis system. Consequently, the spatial
light manipulation means do no longer have to be shifted with
respect to the spectrum of the optical signal but transmission of a
first spectral component and a subsequent transmission of a second
neighboring spectral component of the optical signal can be
effectively realized by reconfiguring of the spatial light
modulator.
[0021] For example, the spatial light modulator can be effectively
realized by an array of individually switchable liquid crystal
cells that are positioned between crossed polarizers. The single
liquid crystal cells can be electrically switched in order to
modify the polarization direction of the incident light. In
combination with the crossed polarizer arrangement a switchable,
hence reconfigurable, spatial transmission mask can be effectively
realized. In this way by appropriately controlling the operation of
the reconfigurable spatial light modulator, specific spectral bands
can be selectively transmitted or blocked. Hence, the
reconfigurable spatial light modulator serves to transmit the at
least first spectral component of the optical signal at the first
time and subsequently serves to transmit the at least second
spectral components of the optical signal at the second time.
Realizing the reconfigurable spatial light modulator as e.g. a
liquid crystal cell arrangement, selective transmission of first
and second spectral components of the optical signal does not
involve any mechanical movement or shifting.
[0022] According to a further preferred embodiment of the
invention, the spatial light manipulation means further comprise an
aperture that has at least a first slit. The width of this at least
first slit is modifiable. By making the width of the transmissive
aperture of the spatial light manipulation means configurable, the
spatial light manipulation means can be individually adapted to a
plurality of different spectral bands featuring spectroscopic peaks
of different width. For example, the width of the transmission
aperture can be modified in such a way that it only allows for
transmission of a single spectroscopic peak. Hence, the at least
first transmitted spectral component may therefore feature a very
narrow spectral band.
[0023] In contrast, the width of the spatial light manipulation
means' aperture may also provide transmission of a fairly broad
spectral band, which is advantageous for acquisition of the
background signal. Typically, the absolute intensity of the
background signal is much larger than the absolute intensity of a
distinct spectroscopic peak. Hence, by increasing the spectral band
of a transmitted spectral component the background contribution of
a detected signal significantly increases. Therefore, as an
alternative to a shifting of the spatial light manipulation means,
its aperture can be extended leading to a significant increase of
the background contribution of the detected signal at the expense
of the spectroscopic contribution. In this way the fairly broadband
transmitted spectral component becomes predominantly representative
of the background signal.
[0024] According to a further preferred embodiment of the
invention, the spatial light manipulation means further comprise at
least a second slit. This second slit also forms an aperture of the
incident spectrally decomposed optical signal. The at least first
and second slit apertures of the spatial light manipulation means
are simultaneously shiftable along the first direction. Typically,
the position of the at least first and second slit apertures of the
spatial light manipulation means correspond to the transverse
position of significant spectral bands of the optical signal. The
at least first and second slit apertures provide transmission of
corresponding spectroscopic peaks at the first time. Hence the
signal acquired by the detector at the first time is representative
of at least two spectroscopic peaks and associate background
contributions. By simultaneously shifting the at least first and
second slit apertures preferably by the same distance along the
first direction, a corresponding second signal can be subsequently
detected by means of the detector at the second time. This second
signal may then be exclusively representative of the superimposed
background noise of the at least first and second spectral
components that were acquired at the first time.
[0025] According to a further preferred embodiment of the
invention, the reconfigurable spatial light modulator is adapted to
form a slit aperture that moves along the first direction. In this
embodiment the reconfigurable spatial light modulator is driven in
e.g. a scanning mode, i.e. the reconfigurable spatial light
modulator serves to subsequently transmit a plurality of adjacent
spectral bands of the entire spectrum. In this way a complete
spectrum featuring spectral peaks and a broad fluorescence and/or
dark current background is segmented into a plurality of contiguous
spectral bands that are subsequently transmitted and recorded by
means of the spatial light modulator and the detector.
[0026] The width of the various segments of the spectrum might be
arbitrarily chosen and might be non uniform. Also the width of the
aperture may dynamically change during a scan through the spectrum.
By segmenting the entire spectrum into a small amount of broadband
segments, such a scan can be performed in a relatively short time
because of the rather small number of segments. This provides a
rather rough estimation of the background level. Alternatively,
such a spectral scan can also be based on a large number of narrow
band spectral segments providing a more reliable determination of
the background level at the expense of a larger time interval
required for a scan of the entire spectrum.
[0027] Furthermore, the position of the at least first slit of the
spatial light manipulation means may arbitrarily vary, e.g. on a
periodical basis. In this way, different spectral bands of the
spectrum may serve as a basis for background compensation which
allows to account for a background that varies in time. Variation
of the position of the at least first slit of the spatial light
manipulation means can either be realized by shifting and/or
reconfiguring the spatial light manipulation means.
[0028] According to a further preferred embodiment of the
invention, the dispersive optical element and the spatial light
manipulation means form a multivariate optical element. Preferably,
the spatial light manipulation means are implemented as a liquid
crystal light modulator or as a digital micro-mirror device (DMD).
Hence, spectrally dispersing the incident optical signal and
directing the evolving spectrum on spatial light manipulation means
allows to selectively attenuate and to block dedicated components
of the spectrum. The spatial light manipulation means may comprise
different spatial light transmission sections, each of which
providing selective transmission of distinct spectral components of
the optical signal.
[0029] For example, the spatial light manipulation means feature a
first and a second spatial light transmission mask effectively
providing wavelength selective transmission that corresponds to
positive and negative parts of a regression function, respectively.
The multivariate optical element can either be realized by means of
a fixed transmission mask that is particularly designed for
analysis of a distinct compound. Alternatively, the spatial light
manipulation means of the MOE can also be implemented as a
reconfigurable arrangement, such as a liquid crystal light
modulator or as a digital micro-mirror device, each of which
providing reconfigurable and selective transmission of various
spectral components of the optical signal.
[0030] According to a further preferred embodiment of the
invention, the optical analysis system is adapted to provide
non-invasive analysis of blood of a person. In this embodiment, the
principal component to be determined by the optical analysis system
is indicative of the concentration of a substance of the blood of
the person. This substance may for example refer to one or more of
the following analytes: glucose, lactate, cholesterol,
oxy-hemoglobin and/or desoxy-hemoglobin, glycohemoglobin (HbAlc),
hematocrit, cholesterol (total, HDL, LDL), triglycerides, urea,
albumin, creatinin, oxygenation, pH, bicarbonate and many
others.
[0031] In another aspect, the invention provides a method of
performing a correction on an optical signal of an optical analysis
system. The inventive method comprises the steps of spatially
separating spectral components of the incident optical signal in a
first direction by means of a dispersive optical element. In a
further step the method comprises at least partially transmitting
at least a first spectral component of the optical signal at a
first time and subsequently at least partially transmitting at
least a second spectral component of the optical signal at a second
time. The partial transmitting of first and second spectral
components is provided by spatial light manipulation means that are
either non-reconfigurable and shiftable or reconfigurable and fixed
in the optical analysis system.
[0032] The at least first and second transmitted spectral
components of the optical signal are detected by means of a
detector. Detection of the at least first and second spectral
components is performed sequentially in order to clearly separate
detection of the at least first and the at least second spectral
components. After detection of the at least first and second
transmitted spectral components, the detected spectral components
are processed, preferably electronically, for performing the
correction on the optical signal. Preferably, the at least first
spectral component refers to a superposition of a spectroscopic
signal of interest and a significant background level, whereas the
at least second spectral components may exclusively represent the
background level of the at least first spectral components.
[0033] According to a further preferred embodiment of the
invention, the method further comprises the steps of at least
partially transmitting at least a third spectral component of the
optical signal at the first time and at least partially
transmitting at least a fourth spectral component of the optical
signal at the second time. Consequently, performing of the
correction of the optical signal is further based on comparing the
at least first, second, third and fourth transmitted and detected
spectral components. In this way, the signal detected at the first
time corresponds to transmission of the at least first and third
spectral components of the optical signal. It is therefore a
superposition of the at least first and third spectral components.
Correspondingly, the second signal detected at the second time
corresponds to a superposition of the at least second and fourth
spectral component of the optical signal. Typically, the at least
first and third spectral components refer to a spectral peak of the
spectrum, whereas the at least second and fourth spectral
components of the optical signal substantially refer to
corresponding background level. In this way, the inventive method
of correcting of the optical signal is by no means limited to the
sequential acquisition of only a first and a second spectral
component. Moreover, the at least first and second spectral
components may constitute a plurality of different spectral
bands.
[0034] In still another aspect, the invention provides a computer
program product for performing a correction on an optical signal of
an optical analysis system. The optical signal is spatially
decomposed into its spectral components by means of a dispersive
optical element. The computer program product comprises computer
program means that are adapted to control spatial light
manipulation means for at least partially transmitting at least a
first spectral component of the optical signal at a first time and
for at least partially transmitting at least a second spectral
component of the optical signal at a second time. The computer
program product further comprises computer program means that are
adapted to process an at least first and second electrical signal
for performing a correction on the optical signal. The at least
first and second electrical signals are provided by a detector in
response to detect the at least first and second transmitted
spectral components of the optical signal.
[0035] It is further to be noted that any reference signs in the
claims are not to be construed as limiting the scope of the present
invention.
[0036] In the following preferred embodiments of the invention will
be described in detail by making reference to the drawings in
which:
[0037] FIG. 1 is a schematic diagram of an embodiment of a blood
analysis system,
[0038] FIGS. 2A and 2B are spectra of the optical signal generated
from blood in the skin and from a sample comprising one analyte in
a solution,
[0039] FIG. 3 is a spectral weighting function implemented in a
multivariate optical element,
[0040] FIG. 4 shows a schematic top view illustration of the
optical analysis system,
[0041] FIG. 5 schematically shows a top view illustration and a
cross section of the spatial light manipulation means,
[0042] FIG. 6 shows a front view illustration of the spatial light
manipulation means in combination with a spectrum,
[0043] FIG. 7 shows an implementation of the spatial light
manipulation means as multivariate optical element having two
transmission sections.
[0044] In the embodiment shown in FIG. 1 the optical analysis
system 20 for determining an amplitude of a principal component of
an optical signal comprises a light source 1 for providing light
for illuminating a sample 2 comprising a substance having a
concentration and thereby generating the principal component. The
amplitude of the principal component relates to the concentration
of the substance. The light source 1 is a laser such as a gas
laser, a dye laser and/or a solid state laser such as a
semiconductor or diode laser.
[0045] The optical analysis system 20 is part of a blood analysis
system 40. The blood analysis system further comprises a
computational element 19 for determining the amplitude of the
principal component, hence for determining the composition of the
compound. The sample 2 comprises skin with blood vessels. The
substance may be one or more of the following analytes: glucose,
lactate, cholesterol, oxy-hemoglobin and/or desoxy-hemoglobin,
glycohemoglobin (HbAlc), hematocrit, cholesterol (total, HDL, LDL),
triglycerides, urea, albumin, creatinin, oxygenation, pH,
bicarbonate and many others. The concentrations of these substances
is to be determined in a non-invasive way using optical
spectroscopy. To this end the light provided by the light source 1
is sent to a dichroic mirror 3 which reflects the light provided by
the light source towards the blood vessels in the skin. The light
may be focused on the blood vessel using an objective 12. The light
may be focused in the blood vessel by using an imaging and analysis
system as described in the international patent application WO
02/057759.
[0046] By interaction of the light provided by the light source 1
with the blood in the blood vessel an optical signal is generated
due to Raman scattering and fluorescence. The optical signal thus
generated may be collected by the objective 12 and sent to the
dichroic mirror 3. The optical signal has a different wavelength
than the light provided by the light source 1. The dichroic mirror
is constructed such that it transmits at least a portion of the
optical signal.
[0047] A spectrum 100 of the optical signal generated in this way
is shown in FIG. 2A. The spectrum comprises a relatively broad
fluorescence background (FBG) 102 and relatively narrow Raman bands
(RB) 104, 106, 108. The x-axis of FIG. 2A denotes the wavelength
shift with respect to the 785 nm of the excitation by light source
1 in wave numbers, the y-axis of FIG. 2A denotes the intensity in
arbitrary units. The x-axis corresponds to zero intensity. The
wavelength and the intensity of the Raman bands, i.e. the position
and the height, is indicative for the type of analyte as is shown
in the example of FIG. 2B for the analyte glucose which was
dissolved in a concentration of 80 mMol in water. The solid line
112 of FIG. 2B shows the spectrum of both glucose and water, the
dashed line 112 of FIG. 2B shows the difference between the
spectrum of glucose in water and the spectrum of water without
glucose. The amplitude of the spectrum with these bands is
indicative for the concentration of the analyte.
[0048] Because blood comprises many compounds each having a certain
spectrum which may be as complex as that of FIG. 2B, the analysis
of the spectrum of the optical signal is relatively complicated.
The optical signal is sent to the optical analysis system 20
according to the invention where the optical signal is analyzed by
a MOE which weights the optical signal by a weighting function
shown e.g. schematically in FIG. 3. The weighting function of FIG.
3 is designed for glucose in blood. It comprises a position part P
and a negative part N. The positive part P and the negative part N
each comprise in this example more than one spectral band.
[0049] Here and in the remainder of this application the distance
between a focusing member and another optical element is defined as
the distance along the optical axis between the main plane of the
focusing member and the main plane of the other optical
element.
[0050] A computational element 19 shown in FIG. 1 is arranged to
calculate the difference between the positive and negative signal.
This difference is proportional to the amplitude of the principal
component of the optical signal. The amplitude of the principal
component relates to the concentration of the substance, i.e. of
the analyte. The relation between the amplitude and the
concentration may be a linear dependence.
[0051] FIG. 4 schematically shows a top view illustration of the
optical analysis system 20. The optical analysis system 20 is
adapted to receive an incident optical beam 18 and to provide an
electronic output to the computational element 19. The optical
analysis system 20 has a grating 22 serving as a dispersive optical
element, a transmission mask 26, a focusing element 28 and a
detector 30. In essence, the grating 22 in combination with the
transmission mask 26 serve as a multivariate optical element
(MOE).
[0052] In this way dedicated spectral components of the incident
optical beam 18 can be filtered and arbitrarily attenuated. By
focusing the spectrally modified optical beam 18 onto the detector
30, a concentration of a particular compound of a substance can be
precisely determined. The transmission pattern of the transmission
mask 26 corresponds to a spectral weighting function that is
specific for each compound to be analyzed by the optical analysis
system 20. Typically, the detector 30 is implemented by means of a
semi conductor based photodiode.
[0053] The invention effectively allows to determine the
concentration of a compound without particularly performing a
complete spectral analysis of the incident light beam 18. Hence, by
making efficient use of the MOE, a rather expensive charge coupled
device (CCD) for recording a complete spectrum 24 of the optical
beam 18 can be effectively replaced by a low cost photodiode
detector 30. The intensity detected by means of the detector 30 is
indicative of a positive and/or negative regression function
realized by the transmission mask 26. By separately detecting
positive and negative parts of a spectral regression function, the
concentration of a compound can be precisely determined. Therefore,
the detector 30 is coupled to the computational element 19 in order
to provide necessary signal processing.
[0054] Preferably, the transmission pattern of the spatial light
transmission mask 26 corresponds to various spectroscopic peaks.
Typically, the transmission pattern of the spatial light
transmission mask 26 is realized by a plurality of slit apertures
featuring a width that corresponds to the narrow spectral bands of
the spectroscopic peaks, e.g. Raman bands 104, 106, 108. In a
configuration where the spectroscopic peaks of the spectrum 24
exactly overlap with corresponding slit apertures of the spatial
light transmission mask 26, a first signal can be detected by means
of the detector 30 that comprises significant contribution from
spectroscopic peaks and associate background signals.
[0055] By slightly shifting the entire spatial light transmission
mask with respect to the position of the spectroscopic peaks of the
spectrum 24, the spectroscopic peaks might be entirely blocked by
means of the spatial light transmission mask 26 and neighboring
spectral bands substantially comprising background signals are
transmitted by the spatial light transmission mask 26 and detected
by the detector 30. In this way two different signals are
sequentially obtained allowing to extract spectroscopic information
of the optical signal 18 from a superimposed first signal providing
spectroscopic information as well as unavoidable broadband
background.
[0056] Shifting of the entire spatial light transmission mask can
in principle be performed on the basis of conventional shifting
means, such like actuators based on piezo technology. Hence, a
lateral displacement of the light transmission mask 26 can be
electrically controlled by means of the processing means 19 that
are typically implemented as a computational device, such as a
personal computer. In this way, the subsequent acquisition of the
at least first and second spectral components of the optical signal
can be autonomously performed without manual instructions from a
user.
[0057] FIG. 5 shows a top view illustration of a similar embodiment
as shown in FIG. 4. Here, a cross section of the spatial light
manipulation means 26 is shown. The spatial light manipulation
means 26 feature an aperture 32 that effectively allows
transmission of a particular spectral component of the spectrum 24.
As indicated by the arrow either the entire light manipulation
means 26 or the aperture 32 can be shifted in the x-direction. In
this way at least first and second spectral components representing
a spectroscopic peak and a background signal can be selectively
transmitted and detected in a sequential way. The spatial light
manipulation means 26 are by no means limited to a single aperture
32. Moreover, the mask 26 may either comprise a plurality of
apertures that are fixed on the transmission mask or the
transmission mask may be implemented as a reconfigurable spatial
light modulator that allows to selectively provide transmission of
various different spectral components.
[0058] When the aperture 32 is fixed on the mask 26, the entire
mask has to be shiftable in the vertical x-direction in order to
sequentially select different spectral components of the spectrum
24. Only when the light transmission mask 26 is implemented as a
reconfigurable spatial light modulator, the mask 26 can be rigidly
mounted with respect to e.g. the dispersive optical element. In an
alternative embodiment, also the dispersive optical element 22
might be implemented as reconfigurable. For example, by modifying
the orientation of the dispersive optical element 22, the spectrum
24 might be vertically shifted on the light transmission mask 26,
thus effectively realizing shifting of a spectroscopic peak with
respect to the aperture 32. Implementing the dispersive optical
element 22 as e.g. rotatable, in principle the transmission mask 26
might also be mounted in the optical analysis system 20 in a
non-moveable way.
[0059] FIG. 6 illustrates a front view of the spatial light
manipulation means with a projected spectrum 100. The spectrum 100
features two spectroscopic peaks 104, 106 and a fairly uniform
broad fluorescence background 102. The transmission aperture 32 is
implemented as a slit aperture. As shown in FIG. 6 the horizontal
width of the aperture 32 substantially matches the width of the
spectral band of the spectroscopic peak 104. The spectroscopic peak
104 corresponds to the Raman band 104 as shown in FIG. 2A. When the
horizontal position of the vertical slit 32 substantially matches
the position of the spectroscopic peak 104, the transmitted
spectral component that can be detected by the detector 30
represents a superposition of the broad fluorescence background 102
and the spectroscopic peak 104.
[0060] In order to resolve the spectroscopic contribution to the
detected signal, a second signal has to be acquired that merely
corresponds to the broad fluorescence background 102. This can be
effectively realized by horizontally shifting the slit 32 to a
position 33 as indicated by the dashed lines. In principle, the
required shifting of the slit 32 can either be realized by shifting
the entire mask 26 in such a way that the position of the slit 32
substantially overlaps with the indicated position 33.
Alternatively, when the spatial light manipulation means 26 are
implemented as a reconfigurable spatial light modulator, such as a
liquid crystal light modulator, the slit 32 can be effectively
moved to the position indicated by the dashed lines 33.
Irrespectively of the implementation of the spatial light
manipulation means 26, the second signal only represents the broad
fluorescence background 102 and therefore allows to extract the
spectroscopic contribution, e.g. the Raman signal of interest, of
the previously acquired spectral component representing a
superposition of a spectroscopic signal and a broad fluorescence
background 102.
[0061] Alternatively or additionally the width of the subsequently
acquired spectral bands can be arbitrarily modified. For example
when the spectrum 100 features a large amount of spectral peaks, it
might be advantageous to acquire a broad fluorescence spectral band
on the basis of a relatively broadband selection. Therefore, the
spectral width of the second transmitted spectral component may
clearly deviate from the spectral width of the first acquired
spectral component. In principle, by increasing the width of a slit
32, the contribution of the background signal to the acquired
signal increases and the portion of the spectroscopic peaks'
contribution decreases.
[0062] Also, when operating in a scanning mode, i.e. the slit 32 is
horizontally moved along the entire transmission mask 26, the width
of the slit 32 has a major impact on the total scanning time. The
larger the slit 32 the faster a scanning can be performed. However,
increasing of the slit width to an extent that is several times
larger than the spectral band of a distinct spectroscopic peak does
no longer allow to precisely measure the intensity of a spectral
peak 104, 106. In practical implementations, it is reasonable to
select a slit width that corresponds a few times the spectral
bandwidth of a spectroscopic peak.
[0063] It is also reasonable to sequentially transmit and to detect
adjacently located spectral bands because the broadband background
might also be subject to modifications over the spectral range of
the spectrum 100. Therefore, the spacing between two subsequent
slit positions should be as small as possible. Otherwise the second
acquired spectral component may refer to a background that strongly
deviates from the background contribution of the previously
acquired spectral component. Since the general structure of a
spectrum 100 is principally known, selection of the at least second
spectral component that is representative of broadband background
can be effectively performed on the basis of the structure of the
spectrum 100. For example, having knowledge that the spectrum 100
features at least two spectroscopic peaks 104, 106, it can be
effectively prevented, that the second spectral component that
shall represent a background signal overlaps with the peak 106.
[0064] FIG. 7 illustrates another embodiment of the transmission
mask 26 featuring two transmission sections 27, 29, each of which
featuring a plurality of slits 34, 36, 38. Here, each slit 34, 36,
38 corresponds to a dedicated spectral component for multivariate
optical analysis. Hence, each of the slits 34, 36, 38 corresponds
to the position of a spectroscopic peak in the spectrum of the
incident optical signal 18. The two transmission sections 27, 29
are adapted to provide positive and negative parts of a regression
function for the multivariate optical analysis, respectively.
Preferably, the width of each slit 34, 36, 38 corresponds to the
width of a corresponding spectroscopic peak. In a first
configuration, the transmission mask 26 effectively provides
transmission of those spectroscopic peaks that correspond to the
horizontal position of the slits 34, 36, 38.
[0065] In this way a positive and a negative regression signal can
be separately detected by means of two vertically positioned
detectors. Preferably, the first detector serves to detect light
being transmitted by the first transmission section 27 and the
second detector is adapted to detect light being transmitted by
means of the second transmission section 29. In a second
configuration, the horizontal position of the slits 34, 36, 38 is
slightly shifted with respect to the first configuration in order
to block the corresponding spectroscopic peaks and to transmit an
adjacently located spectral band being indicative of broad
fluorescence background. Here, both transmission sections 27, 29
can be shifted simultaneously either by an appropriate
reconfiguration of the spatial light transmission mask 26 or by
shifting a fixed transmission pattern, e.g. by shifting the entire
mask 26 in a horizontal direction. In this way a background signal
of each positive and negative part of a regression function can be
separately obtained allowing to separately correct positive and
negative parts of the regression function.
[0066] The present invention therefore provides effective means for
sequentially acquiring a first and a second signal that allow for
background compensation of a spectroscopic signal. Preferably, the
first acquired optical signal features a background and a
spectroscopic contribution and the second optical signal only
features a background that corresponds to the background
contribution of the first signal. Selection of various spectral
components of the incident optical signal 18 can be effectively
performed by making use of the multivariate optical element. In
particular, the sequential selection of spectroscopic and
background signals can be effectively implemented into existing
spectroscopic analysis systems making use of multivariate optical
elements. Selection of the spectral component that is indicative of
a broadband background level can be effectively realized either by
reconfiguration of a spatial light transmission mask or by a slight
displacement of the entire spatial light transmission mask.
List of Reference Numerals
[0067] 1 light source
[0068] 2 sample
[0069] 3 dichroic mirror
[0070] 12 objective
[0071] 18 optical beam
[0072] 19 computer
[0073] 20 optical analysis system
[0074] 22 grating
[0075] 24 spectrum
[0076] 26 transmission mask
[0077] 27 transmission section
[0078] 28 focusing element
[0079] 29 transmission section
[0080] 30 detector
[0081] 32 slit
[0082] 34 slit
[0083] 36 slit
[0084] 38 slit
[0085] 40 blood analysis system
[0086] 100 spectrum
[0087] 102 broad fluorescence background
[0088] 104 Raman band
[0089] 106 Raman band
[0090] 108 Raman band
[0091] 110 combined spectrum
[0092] 112 glucose spectrum
* * * * *